This project aims to understand cellular interactions in man which result in basophil and mast cell activation by analyzing the capacity of macrophages to secrete factor(s) which induce mediator release from basophils and mast cells. It will extend recent observations that cultured human lung macrophages produce soluble factor(s) which are potent inducers of histamine release from human basophils, and less potent inducers of histamine and PGD2 release from lung mast cells; and that the predominant histamine releasing activity is an IgE-binding factor. The grant aims to identify the subpopulations of macrophages which produce histamine releasing activities, to define the stimuli which induce macrophages to produce these activities, to purify and identify the factor(s) (derived from macrophages and macrophage cell lines like U937 cells) which are responsible for the activities. It also aims to examine the mechanism of action of the factors on mast cells and basophils, and determine the spectrum of mediators released from target cells. An additional aim of the grant is to extend recent studies indicating that during late (3-8 hrs. after antigen) IgE-mediated reactions induced by nasal challenge with antigen, nasal wash samples contain not only histamine, but also a histamine releasing activity, and that this activity may be, at least in part, and IgE-binding factor. Further studies will characterize the activity and determine whether it is similar to the activities produced by cultured macrophages. These studies should help to define the interactions between human macrophages and mast cells and basophils, which are likely to be physiologically important during a variety of inflammatory reactions containing these cells, particularly cell-mediated immune reactions and the late phase of IgE-mediated inflammation. They also will determine whether macrophage-derived histamine releasing activities are produced in vivo during such inflammatory reactions.